Leukemia is a progressive, malignant disease of the blood-forming organs, characterized by the abnormal proliferation and development of leukocytes, and their precursors in the blood and bone marrow. The disease is classified clinically on the basis of (1) whether the condition is acute or chronic, (2) whether it involves myeloid (i.e. myelogenous), lymphoid (non-myelogenous) or monocytic cells, and (3) whether it is associated with an increase in the concentration of abnormal cells in the blood.
A characteristic of leukemia is the presence of specific chromosomal abnormalities which are considered to be involved in tumor development (Rabbitts, T., Cell 67:641-644 (1991); Cleary, M. L., Cell 66:619-622 (1991), both herein incorporated by reference). In acute leukemia, such chromosomal abnormalities frequently activate transcription factors. These factors are often important in differentiation. Thus, for example, the activation of the c-myc gene, is associated with T-cell acute leukemia.
The best studied leukemic translocation is that which results in the presence of the Philadelphia chromosome, and has been found to be indicative of chronic myelogenous leukemia. This translocation fuses the c-ABL gene with BCR, a transcription unit on chromosome 22. The chimeric protein that results has been found to have growth promoting tyrosine kinase activity (Sawyers, C. L. et al., Cell 64:337-350 (1991)). Other well characterized translocations include the translocation of chromosomes 15 and 17, and 6 and 9, that are characteristic of acute promyelocytic leukemia, and acute myeloid leukemia, respectively (Borrow, J. et al., Science 249:1577-1580 (1990); de Th e, H. et al., Nature 347:558-561 (1990); Alcalay, M. et al., Proc. Natl. Acad. Sci. (U.S.A.) 88:1977-1981 (1991); von Lindern, M. et al., Molec. Cell, Biol. 10:4016-4026 (1990)).
The M2 and M1 AML is presently diagnosed using cytogenetic methods, and in particular, through karyotypic analysis of the chromosome 8 - 21 translocation. In general, the method is time consuming, and thus delays a conclusive diagnosis. Moreover, due to the nature of karyotypic analysis, the method requires highly trained technicians. More significantly, since karyotypic analysis can be effectively done only on small numbers of cells (e.g. 20-50 cells), and leukemic cells are present at a low concentration (relative to non-leukemic cells), the method is generally incapable of detecting a leukemic condition that affects less than 2-5% of the cells analyzed. It thus has significant drawbacks for monitoring the results of chemotherapy or tumor proliferation. Thus, a more rapid method for identifying individuals having a chromosomal 8-21 translocation would be highly desired. The present invention provides such a method.